Angiotensin II Increases Oxidative Stress and Inflammation in Female, But Not Male, Endothelial Cells.

IF 2.3 4区医学 Q3 BIOPHYSICS Cellular and molecular bioengineering Pub Date : 2023-04-12 eCollection Date: 2023-04-01 DOI:10.1007/s12195-023-00762-2

Callie M Weber, Mikayla N Harris, Sophia M Zic, Gurneet S Sangha, Nicole S Arnold, Douglas F Dluzen, Alisa Morss Clyne

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Abstract

Introduction: Women are at elevated risk for certain cardiovascular diseases, including pulmonary arterial hypertension, Alzheimer's disease, and vascular complications of diabetes. Angiotensin II (AngII), a circulating stress hormone, is elevated in cardiovascular disease; however, our knowledge of sex differences in the vascular effects of AngII are limited. We therefore analyzed sex differences in human endothelial cell response to AngII treatment.

Methods: Male and female endothelial cells were treated with AngII for 24 h and analyzed by RNA sequencing. We then used endothelial and mesenchymal markers, inflammation assays, and oxidative stress indicators to measure female and male endothelial cell functional changes in response to AngII.

Results: Our data show that female and male endothelial cells are transcriptomically distinct. Female endothelial cells treated with AngII had widespread gene expression changes related to inflammatory and oxidative stress pathways, while male endothelial cells had few gene expression changes. While both female and male endothelial cells maintained their endothelial phenotype with AngII treatment, female endothelial cells showed increased release of the inflammatory cytokine interleukin-6 and increased white blood cell adhesion following AngII treatment concurrent with a second inflammatory cytokine. Additionally, female endothelial cells had elevated reactive oxygen species production compared to male endothelial cells after AngII treatment, which may be partially due to nicotinamide adenine dinucleotide phosphate oxidase-2 (NOX2) escape from X-chromosome inactivation.

Conclusions: These data suggest that endothelial cells have sexually dimorphic responses to AngII, which could contribute to increased prevalence of some cardiovascular diseases in women.

Supplementary information: The online version contains supplementary material available at 10.1007/s12195-023-00762-2.

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血管紧张素 II 会增加雌性内皮细胞的氧化应激和炎症反应，但不会增加雄性内皮细胞的氧化应激和炎症反应。

导言：女性罹患某些心血管疾病的风险较高，包括肺动脉高压、老年痴呆症和糖尿病血管并发症。血管紧张素 II（AngII）是一种循环应激激素，在心血管疾病中会升高；然而，我们对 AngII 对血管影响的性别差异了解有限。因此，我们分析了人类内皮细胞对 AngII 处理反应的性别差异：方法：用 AngII 处理男性和女性内皮细胞 24 小时，并对其进行 RNA 测序分析。然后，我们使用内皮和间质标记物、炎症检测和氧化应激指标来测量雌性和雄性内皮细胞对 AngII 的功能变化：我们的数据显示，雌性和雄性内皮细胞在转录组上是不同的。经 AngII 处理的雌性内皮细胞与炎症和氧化应激通路相关的基因表达发生了广泛变化，而雄性内皮细胞的基因表达几乎没有变化。虽然雌性和雄性内皮细胞在接受 AngII 处理后都能保持内皮表型，但雌性内皮细胞在接受 AngII 处理后，炎症细胞因子白细胞介素-6 的释放量增加，白细胞粘附性增加，同时还伴有第二种炎症细胞因子。此外，与雄性内皮细胞相比，雌性内皮细胞在接受 AngII 处理后活性氧生成增加，其部分原因可能是烟酰胺腺嘌呤二核苷酸磷酸氧化酶-2（NOX2）从 X 染色体失活中逃脱：这些数据表明，内皮细胞对AngII的反应具有性别双态性，这可能是导致某些心血管疾病在女性中发病率增加的原因之一：在线版本包含补充材料，可在 10.1007/s12195-023-00762-2 网站上查阅。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cellular and molecular bioengineering 生物-生物物理

CiteScore

5.60

自引率

3.60%

发文量

审稿时长

>12 weeks

期刊介绍： The field of cellular and molecular bioengineering seeks to understand, so that we may ultimately control, the mechanical, chemical, and electrical processes of the cell. A key challenge in improving human health is to understand how cellular behavior arises from molecular-level interactions. CMBE, an official journal of the Biomedical Engineering Society, publishes original research and review papers in the following seven general areas: Molecular: DNA-protein/RNA-protein interactions, protein folding and function, protein-protein and receptor-ligand interactions, lipids, polysaccharides, molecular motors, and the biophysics of macromolecules that function as therapeutics or engineered matrices, for example. Cellular: Studies of how cells sense physicochemical events surrounding and within cells, and how cells transduce these events into biological responses. Specific cell processes of interest include cell growth, differentiation, migration, signal transduction, protein secretion and transport, gene expression and regulation, and cell-matrix interactions. Mechanobiology: The mechanical properties of cells and biomolecules, cellular/molecular force generation and adhesion, the response of cells to their mechanical microenvironment, and mechanotransduction in response to various physical forces such as fluid shear stress. Nanomedicine: The engineering of nanoparticles for advanced drug delivery and molecular imaging applications, with particular focus on the interaction of such particles with living cells. Also, the application of nanostructured materials to control the behavior of cells and biomolecules.